Disease relevance of mestranol

• The women with adenomas took mestranol-containing pills much more commonly than the controls (P less than 0.0001) [1].
• Three dogs had single malignant mammary nodules, 3 dogs had 2 malignant nodules, 2 dogs had 4-6 malignant nodules, and 1 dog in the treatment group given high dosages of ethynerone plus mestranol had 14 mammary nodules composed of fibrosarcoma [2].
• Five to nine weeks later, the animals were ovariectomized, allowed to recover, and administered daily doses of CR extract (0.714, 7.14, or 71.4 mg/kg body weight per day) or control substances (estrogen/positive control: 450 microg/kg/day mestranol; or CR vehicle/negative control) [3].
• The hepatocellular carcinoma incidence was significantly increased at the high mestranol dose [4].
• Chronic mestranol treatment also provoked Leydig cell hyperplasia; this is most probably due to induction of liver metabolism of mestranol to ethinylestradiol [5].

High impact information on mestranol

• 17 alpha-Estradiol, mestranol, and estriol did not significantly alter the levels of estrogen receptor in cytosol or nuclei [5].
• At 9 months, in diethylnitrosamine-initiated rats, ethinyl estradiol and mestranol caused 3.5- and 4.4-fold increases, respectively, in the number of GGT lesions per liver and an increased incidence of hepatocellular carcinomas while estradiol had no enhancing effect [4].
• Small increases in the numbers of larger GGT lesions were also observed in noninitiated animals treated with mestranol and ethinyl estradiol and are most probably due to promotion of spontaneously initiated hepatocytes [4].
• The morphologic effects of synthetic reproductive steroids on the mammary gland of rhesus monkeys. Mestranol, ethynerone, mestranol-ethynerone, chloroethynyl norgestrel-mestranol, and anagestone acetate-mestranol combinations [6].
• The mestranol and ethynerone combination produced a proliferative atypia in 22 of 52 animals (42%), including five identical to intraductal carcinoma in the human and one identical to lobular neoplasia [6].

Chemical compound and disease context of mestranol

• The chloroethynyl norgestrel and mestranol combination induced proliferative atypia in 25 of 52 monkeys (49%); six of these atypias were severe and indistinguishable from intraductal carcinoma of the human breast; and one, if in the human breast, would reflect a solid variant of an invasive carcinoma [6].
• The results show that: mestranol and norethynodrel can promote DEN-initiated hepatocarcinogenesis, as indicated by increased numbers of gamma-glutamyl transpeptidase-positive, putative preneoplastic lesions and by the appearance of carcinomas [7].
• Two of them were taking unopposed estrogens and developed cystic hyperplasia; the other patient, treated with norethindrone in addition to mestranol, disclosed focal cystic glandular hyperplasia [8].
• A prospective study was undertaken to determine the effect on liver function tests of a combined oral contraceptive containing norethisterone 1 mg and mestranol 0.05 mg, in women with schistosomiasis japonica in Leyte, Philippines [9].
• Injections of bradykinin at 0.1, 0.3, and 1.0 microgram/100 gm body weight decreased mean arterial pressure significantly more in 10 mestranol-treated rats than in 10 control rats [10].

Biological context of mestranol

• Mestranol at 10(-6) M preferentially stimulated angiotensinogen production 5-fold, whereas cell growth rate was slightly increased [11].
• Hepatogenotoxicity was assessed in two ways, first using alkaline elution to detect liver DNA damage after in vivo treatment with mestranol, and second by detection of DNA repair synthesis in primary cultures of hepatocytes treated with various oral contraceptive steroids [12].
• Comparable results were obtained for thymidine uptake in the course of the cell cycle, with a maximum increase for 10(-5) M mestranol, and an increase of angiotensinogen production for 10(-6) M mestranol [11].
• Analysis of the time course of the pressor response indicates that mestranol treatment altered the duration of the blood pressure increase without an apparent change in the onset of the pressor response [13].
• Administration of PGF-analog and mestranol in the third trimester terminated pregnancy in only 1 of 3 monkeys [14].

Anatomical context of mestranol

• An increase in erythrocyte zinc was observed due to "Norinyl." No effect of oral contraceptive agents on plasma calcium, magnesium and erythrocyte magnesium was observed [15].
• The synthetic estrogens ethinylestradiol (17 alpha-ethynyl-1,3,5-estratriene-3,17 beta-diol) and mestranol [3-methoxy-17 alpha-ethinyl-1,3-5(10)-estratiene-17 beta-OL] are competitors for the estrogen receptor in the human Fallopian tube [16].
• In competition experiments, ethinylestradiol (EE2) and mestranol were able to inhibit [3H]DEX binding to microsomes, whereas natural estrogens, tamoxifen or estrogen sulfates were ineffective [17].
• Results of this investigation demonstrated that 17beta-estradiol and the estrogenic steroids estrone, estriol, mestranol, and equilin induced significant increases in cortical nerve cell growth [18].
• Effects of the climacteric and sequential mestranol and norethisterone on the cervix and genital tract [19].

Associations of mestranol with other chemical compounds

• Several alpha and beta adrenergic responses were studied in female rats after treatment with a low dose of the synthetic estrogen, mestranol (15 micrograms i.p. biweekly), for 4 to 6 weeks and compared with untreated controls [13].
• Oral contraceptive steroids, norethynodrel and mestranol, were fed to 11-wk-old female Sprague-Dawley rats, in combination and in quantities proportional to those used by women for contraceptive purposes [20].
• In contrast, the half-time of the blood pressure response was significantly prolonged after administration of the various concentrations of norepinephrine to mestranol-treated rats [13].
• The effluent from the silica column was monitored serially with a fixed-wavelength UV detector (254 nm) for norethindrone quantitation and a fluorescence detector (230 nm for excitation and 280 nm cutoff filter for emission) for mestranol quantitation [21].
• Before treatment the squamocolumnar junction was visible in only six of the 12 women, but after treatment with sequential mestranol and norethisterone the squamocolumnar junction became visible due to a minor degree of eversion [19].

Gene context of mestranol

• Zafirlukast deserves further clinical study as an inhibitor of other CYP2C9 substrates such as nonsteroidal anti-inflammatory agents, tolbutamide, phenytoin and mestranol [22].
• The mRNAs of both MCSF and c-fms proto-oncogene were induced in the uterine myometrium of non-pregnant women under pseudopregnant therapy of mestranol and norethindrone [23].
• Levels of oxytocin (OT) were found to be normal and unstimulated after cigarette inhalation in two subjects, but when two affected male siblings ingested Ovulen, OT and ESN were stimulated to subnormal levels [24].
• Inhibition of oviductal estrogen binding is 500 times greater with ethinylestradiol than with mestranol (ki = 0.75 X 10(-9) M for ethinylestradiol; Ki = 3.74 X 10(-7) M for mestranol) [16].
• The thyrotrophin (TSH) responses to thyrotrophin releasing hormone (TRH) in 16 oophorectomised postmenopausal women on long term treatment with mestranol 24 micrograms daily were compared to those in 16 oophorectomised postmenopausal women on placebo treatment [25].

Analytical, diagnostic and therapeutic context of mestranol

• An intravenous glucose tolerance test (GTT) was given to 116 women--82 nondiabetic subjects (NDS) and 34 diabetes suspects--before they received Ovulen for oral contraception [26].
• A procedure is described for the assay of ethynodiol diacetate and ethinyl estradiol/mestranol by HPLC using two UV detectors at 210 and 280 nm [27].
• Quantitative analysis of ethynodiol diacetate and ethinyl estradiol/mestranol in oral contraceptive tablets by high-performance liquid chromatography [27].
• The coagulation profile of oophorectomised women on long-term (15 yr) hormone replacement therapy with mestranol (30 micrograms/day) is compared to that of women on long-term placebo [28].
• Twenty-nine menstrual age women who had a hysterectomy and oophorectomy were treated cyclically with 80 micrograms of mestranol per day for 2 yr [29].

References